Porous, Hollow, and Ball-in-Ball Metal Oxide Microspheres: Preparation, Endocytosis, and Cytotoxicity

Current technology relies heavily on composite materials, but in most cases, the size of the individual components have been micrometers or larger. The development of nanotechnology is driven in part by the desire to prepare materials that are only a few nanometers in size or that are made from components in the sub-micrometer regime. Improved preparations of various examples of monodisperse, porous, hollow, and/or core/shellmetal and semiconductor nanoparticles or nanowires have been developed. We report here the use of a simple and scalable technology, ultrasonic spray pyrolysis (USP), to prepare porous, hollow, or ball-in-ball nanomaterials (Fig. 1 and Supporting Information Fig. S1). In addition, we have investigated the cell toxicity (cytotoxicity) of these nanomaterials, in keeping with the growing concern of health effects that manmade nanoparticles could have now and in the near future. Our interest in USP stems from our long standing work on the chemical and physical effects of ultrasound. In liquids irradiated with high-intensity ultrasound, acoustic cavitation produces high-energy chemistry through intense local heating inside the gas phase of collapsing bubbles in the liquid. There are diverse applications of such sonochemistry, including the preparation of nanostructured materials and nanoparticles. USP presents an interesting inversion of the cavitation process. Both confine the chemical reactions to isolated sub-micrometer reaction zones, but sonochemistry does so in a heated gas phase within a liquid, while USP uses a hot liquid droplet (or resulting heated solid particle) carried by a gas flow. Thus, we view USP as a method of phase-separated synthesis, in our cases, using sub-micrometer-sized droplets as isolated chemical reactors for nanomaterial synthesis. While USP has been used to create both titania and silica spheres separately, there are no prior reports of titania– silica composites. We have now produced such nanocomposites, and by further manipulation, generated various porous structures with fascinating morphologies (Figs. 1 and 2 and Supporting Information Fig. S3). As described in more detail in the Experimental section, a precursor solution was nebulized using a commercially available household ultrasonic humidifier (1.7 MHz ultrasound generator), and the resulting mist was carried in a gas stream through a glass tube in a hot furnace. After exiting the hot zone, spherical particles a few hundred nanometers in size (hereon referred to as microspheres) were collected in a water-filled bubbler as an aqueous colloidal solution. The microspheres were then isolated from this solution by centrifugation. Morphology, size distribution, and composition were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning TEM (STEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Cytotoxicity was tested with several whole mammalian cell assays. Small molecules were also delivered inside through the endocytosis of microspheres. C O M M U N IC A TI O N S